P1165: BETALUTIN® IN PATIENTS WITH RELAPSED/ REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) NOT ELIGIBLE FOR AUTOLOGOUS STEM CELL TRANSPLANT
Authors: T. Illidge, M. Beasley, J. G. Codina, F. Cavallo, V. Pascal, V. Wills
Journal: HemaSphere (2022)

Background: There remains a significant unmet medical need for the treatment of patients with relapsed/refractory DLBCL. Betalutin® (lilotomab labelled with the beta-emitter 177Lu), targets the CD37 antigen which permits delivery of a therapeutic dose of radiation directly to the DNA of tumour cells. Betalutin® is under development for the treatment of relapsed/refractory Non-Hodgkin's Lymphoma (NHL). Aims: This was an open label Phase I, multi-centre, single ascending dose study of four different treatment regimens of Betalutin® administered after rituximab pre-treatment and lilotomab pre-dosing. The purpose of this study was to define the maximum tolerated dose (MTD) of Betalutin®. Methods: Eligible participants received 375 mg/m2 rituximab on Day -14 and escalating doses of both lilotomab (60 and 100 mg/m2) and Betalutin® (10, 15 and 20 MBq/kg) on Day 0. Participants were followed-up for dose limiting toxicities (DLTs) for up to 12 weeks. Participants were followed-up until disease progression, the start of further anticancer treatment or until withdrawal from the study for any reason. Tumour response was determined using Cheson et al, 2014. Clinical benefit was assessed using the ECOG performance and quality of life (QoL) assessments using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) scale. Results: A total of 16 participants (8 males and 8 females) with median age 75 years (range: 45 to 94 years) received lilotomab and Betalutin® after pre-treatment with rituximab. Overall ECOG scores at screening was 0 in 5 (31.3%), 1 in 7 (43.8%) and 2 in 4 (25.0%) participants. DLBCL stage at screening was Stage III or IV in 13 (81.3%). Median time since last relapse was 1.3 months, and 11 (68.8%) participants were refractory to the last anti-lymphoma therapy. Cell surface expression of CD37 on tumour cells was demonstrated for all patients before treatment. A single case of DLT (grade 4 neutropenia) was reported in an 83-year-old female at the dose of 100 mg/m2 lilotomab and 20 MBq/kg Betalutin® on day 43; there was no fever or infections associated with neutropenia; the event was treated with filgastrim and resolved after 2 weeks on day 57. A total of 14 (87.5%) participants had at least one treatment emergent adverse event (TEAE). Most events occurred between Days 1-92 and the most commonly reported events (in 4 [25.0%] participants each) were diarrhoea, decrease in lymphocyte count, and decrease in neutrophil count. Grade ≥3 TEAEs were reported in 10 (62.5%) participants, of which only four (25.0%) participants had treatment related events (decrease in lymphocyte count - 2 participants, decrease in neutrophil count - 1 participant and decrease in white blood cell count -1 participant). No SAEs assessed were deemed to be related to lilotomab and Betalutin®, by the investigators. Nine (56.3%) deaths were reported, all were determined to be related to disease progression and none was considered related to the study drugs. Two participants (one each from the 2 highest dose cohorts) had complete responses that lasted 2.8 and 3.0 months, respectively. Summary/Conclusion: Betalutin® is well tolerated in relapsed/ refractory DLBCL and a MTD was not reached in this study. The initial efficacy and safety findings from this study warrant further investigation of Betalutin® as a single agent or in combination with a standard of care treatment in relapsed/refractory DLBCL. References: Cheson et al, J Clin Oncol 2014:32: 3059-67